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Prevalence and characteristics of screen-detected prostate carcinomas at low PSA levels: aggressive or insignificant?

Created: 4/4/2005


Prevalence and characteristics of screen-detected prostate carcinomas at low PSA levels: aggressive or insignificant?

C Gosselaar, M J Roobol, F H Shroder

BJUInt 95: 231-237


  • Carcinoma of the prostate (CaP) is the most common neoplasm in men and the second most cause of cancer death in western men.
  • Optimum threshold PSA value for prostate biopsy remains unknown. Too high and important cancers may be missed. Too low increases number of unnecessary biopsies and number of insignificant cancers.
  • Screening for CaP at low PSA levels (£4ng/ml) risks detecting clinically insignificant cancers (AKA autopsy, latent, incidental or histological). Slow progression, advanced age at diagnosis and co-morbidities mean that many patients die from intercurrent disease before CaP becomes progressive.
  • Estimated lifetime risk of developing CaP for 50-yr old American man 42%, lifetime risk of a clinically detected CaP @ 9.5%, risk of death from CaP 2.9% [1, 2].
  • Clinically insignificant CaP’s tend to be small volume, well differentiated and not invasive. Some authors have classified tumours as insignificant if <0.2ml, confined to prostate and Gleason score (GS) <7[3].
  • The current paper compares positive predictive value (ppv)/prevalence and tumour characteristics in a side study of the Prostate Cancer Prevention Trial (PCPT)[4] with the European Randomised study of Screening for Prostate Cancer (ERSPC)[5], cystoprostectomy- and autopsy series in order to investigate whether screening at low PSA values leads to the detection of insignificant carcinomas. They use biopsy results from the ERSPC for comparison because of their similarity in PSA levels. Cystoprostectomy- and autopsy series are used as they are considered incidental.
  • The side study by Thompson et al was carried out on participants in the placebo arm of the PCPT. The 2950 subjects never had a PSA = 4 or an abnormal DRE. CaP was diagnosed in 15.2%, of whom 14.9% had a GS of =7. The prevalence of CaP increased with PSA, as did the prevalence of high-grade cancers. They concluded that biopsy-detected CaP (including high-grade) is not rare in men with PSA’s <4 and even <2.


Prevalence and PPV

The ppv (number of CaP’s divided by number of men biopsied) of ERSPC compared to PCPT is hown in the table below. At low PSA’s the ppv in the PCPT is higher than the ERSPC.




3.1-4.0 ng/ml



2.1-3.0 ng/ml



1.1-2.0 ng/ml



<1 ng/ml



The prevalence of CaP in the PCPT was 15.2% compared to 12-54% for autopsy studies and 23-46% for cystoprostatectomy series. The higher prevalence rate in autopsy and cystoprostatectomy series may be related to the fact that the whole prostate is examined in these studies.

Tumour characteristsics

Biopsy identifies 3 prognostic groups; GS6,7 and 8-10 (all lower scores are included in 6)[3]. The probability of histological progression (capsular penetration, seminal vesical infiltration and micrometz to pelvic lymph nodes, is related to intracapsular tumour volume (TV). Tmours are classified as insignificant if <0.2ml, confined to prostate and Gleason score (GS) <7. The present authors found it particularly difficult to compare tumour aggressiveness (i.e. GS and TV) between the PCPT and other studies, however:

  • In the PCPT 14.9% of CaP’s were GS 7-10 compared with 14.3% in the ERSPC. However, the ERSPC included PSA’s between 2-3.9 whereas the PCPT included PSA’s of 0-4. Therefore if PSA’s in the lowest range were included in the ERSPC figures, the detection rate would be lower.
  • The current review found it difficult to compare the PCPT to autopsy series. However, in 1 study there was a similar percentage of poorly to undifferentiated CaP’s compared to the PCPT. This suggests a resemblance of PCPT to autopsy studies.
  • Only one of the cystoprostectomy series compared to the PCPT had a similar percentage of poorly differentiated tumours, however these were small and confined to the prostate thereby resembling autopsy cancers.


Thompson et al concluded that biopsy-detected CaP (including high-grade) is not rare in men with PSA’s <4 and even <2. The current paper found some difficulty comparing prevalence and aggressiveness of CaP’s in the PCPT to associated literature. However, where comparison was possible findings contradict those of the PCPT. Favourable characteristics of CaP’s detected at low PSA’s justify the conclusion that a significant proportion of CaP’s found at routine biopsy are clinically insignificant and similar to autopsy cancers. These observations put the value of screening men with low PSA values (i.e. less than 3ng/ml) in question. A threshold of 3 may produce a good balance between an acceptable PPV of the test and detecting clinically significant CaP’s.

1. Scardino, P., R. Weaver, and M. Hudson, Early detection of prostate cancer. Hum Pathol, 1992. 23(3): p. 211-222.

2. Scardino, P., Early detection of prostate cancer. Urol Clin North Am, 1989. 16(4): p. 635-655.

3. Epstein, J., et al., Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA, 1994. 271(368-374).

4. Thompson, I. and e. al, Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med, 2004. 350(22): p. 2239-46.

5. Raaijmakers, R. and e. al, Prostate cancer detection in the prostate specific antigen range of 2.0 to 3.9 ng/ml: value of percent free prostate specific antigen on tumor detection and tumor aggressiveness. J Urol, 2004. 171(6 Pt 1): p. 2245-2249.

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